Source:http://linkedlifedata.com/resource/pubmed/id/20172594
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2010-3-26
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| pubmed:abstractText |
Calmodulin (CaM) antagonists induce apoptosis in various tumor models and inhibit tumor cell invasion and metastasis, thus some of which have been extensively used as anti-cancer agents. In platelets, CaM has been found to bind directly to the cytoplasmic domains of several platelet receptors. Incubation of platelets with CaM antagonists impairs the receptors-related platelet functions. However, it is still unknown whether CaM antagonists induce platelet apoptosis. Here we show that CaM antagonists N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W7), tamoxifen (TMX), and trifluoperazine (TFP) induce apoptotic events in human platelets, including depolarization of mitochondrial inner transmembrane potential, caspase-3 activation, and phosphatidylserine exposure. CaM antagonists did not incur platelet activation as detected by P-selectin surface expression and PAC-1 binding. However, ADP-, botrocetin-, and alpha-thrombin-induced platelet aggregation, platelet adhesion and spreading on von Willebrand factor surface were significantly reduced in platelets pre-treated with CaM antagonists. Furthermore, cytosolic Ca(2+) levels were obviously elevated by both W7 and TMX, and membrane-permeable Ca(2+) chelator BAPTA-AM significantly reduced apoptotic events in platelets induced by W7. Therefore, these findings indicate that CaM antagonists induce platelet apoptosis. The elevation of the cytosolic Ca(2+) levels may be involved in the regulation of CaM antagonists-induced platelet apoptosis.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1,2-bis(2-aminophenoxy)ethane...,
http://linkedlifedata.com/resource/pubmed/chemical/Calmodulin,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Egtazic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/P-Selectin,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylserines,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet Aggregation Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Tamoxifen,
http://linkedlifedata.com/resource/pubmed/chemical/Thrombin,
http://linkedlifedata.com/resource/pubmed/chemical/Trifluoperazine,
http://linkedlifedata.com/resource/pubmed/chemical/von Willebrand Factor
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| pubmed:status |
MEDLINE
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| pubmed:month |
Apr
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| pubmed:issn |
1879-2472
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| pubmed:author | |
| pubmed:copyrightInfo |
(c) 2010 Elsevier Ltd. All rights reserved.
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| pubmed:issnType |
Electronic
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| pubmed:volume |
125
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
340-50
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| pubmed:meshHeading |
pubmed-meshheading:20172594-Apoptosis,
pubmed-meshheading:20172594-Blood Platelets,
pubmed-meshheading:20172594-Calmodulin,
pubmed-meshheading:20172594-Carrier Proteins,
pubmed-meshheading:20172594-Caspase 3,
pubmed-meshheading:20172594-Egtazic Acid,
pubmed-meshheading:20172594-Humans,
pubmed-meshheading:20172594-Membrane Potentials,
pubmed-meshheading:20172594-Mitochondria,
pubmed-meshheading:20172594-P-Selectin,
pubmed-meshheading:20172594-Phosphatidylserines,
pubmed-meshheading:20172594-Platelet Activation,
pubmed-meshheading:20172594-Platelet Aggregation,
pubmed-meshheading:20172594-Platelet Aggregation Inhibitors,
pubmed-meshheading:20172594-Tamoxifen,
pubmed-meshheading:20172594-Thrombin,
pubmed-meshheading:20172594-Trifluoperazine,
pubmed-meshheading:20172594-von Willebrand Factor
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| pubmed:year |
2010
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| pubmed:articleTitle |
Calmodulin antagonists induce platelet apoptosis.
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| pubmed:affiliation |
School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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